Holley Christopher T, Long Eric K, Butterick Tammy A, Duffy Cayla M, Lindsey Megan E, Stone Laura Hocum, McFalls Edward O, Kelly Rosemary F
Department of Surgery, University of Minnesota, Minneapolis, Minnesota.
Geriatric Research and Clinical Center (GRECC), Minneapolis Veterans Affairs Health Care System (VAHCS), Minneapolis, Minnesota; Department of Food Science and Nutrition, University of Minnesota, Minneapolis, Minnesota.
J Surg Res. 2015 May 1;195(1):29-36. doi: 10.1016/j.jss.2014.12.052. Epub 2015 Jan 7.
Hibernating myocardium is characterized by viable yet dysfunctional myocardium secondary to chronic ischemia, with studies demonstrating incomplete early recovery after coronary artery bypass graft (CABG). We tested whether mitochondrial fusion proteins, an indicator of mitochondrial biogenesis, are increased in hibernating myocardium post-CABG.
A constrictor was placed on the left anterior descending (LAD) artery of nine pigs. Four of these pigs additionally underwent CABG 12 wk later with a left internal mammary artery graft to the LAD distal to the constrictor. Five pigs had a constrictor placed but did not undergo CABG (Hib). Five pigs did not have a constrictor placed (control). Computerized tomography angiography was used to confirm stenosis at the site of constrictor placement and patency of left internal mammary artery grafts. Regional blood flows were determined at baseline and during 40 μg/kg/min dobutamine infusion. Mitochondrial proteins were quantified by Western blot.
Blood flow in the LAD region after CABG was lower than remote regions during dobutamine infusion (2.54 ± 0.24 versus 3.46 ± 0.33 mL/min/g; P < 0.05). Electron transport chain proteins were ∼70% lower in Hib compared with those in control and failed to normalize after CABG. Post-CABG, PGC1α nuclear-bound content was increased compared with Hib (9.02 ± 0.48 versus 5.54 ± 0.98 arbitrary units, respectively; P < 0.05), and expression of mitofusins-1 and 2 and optic atrophy-1 more than doubled.
PGC1α and mitochondrial fusion proteins are increased 4 wk post-CABG in hibernating hearts, indicating mitochondrial fusion has begun to occur and signaling early mitochondrial recovery. Future studies should address changes in maximal myocardial oxygen consumption relative to mitochondrial protein expression.
冬眠心肌的特征是继发于慢性缺血的存活但功能失调的心肌，研究表明冠状动脉旁路移植术（CABG）后早期恢复不完全。我们测试了线粒体融合蛋白（线粒体生物合成的一个指标）在CABG后的冬眠心肌中是否增加。
在9头猪的左前降支（LAD）动脉上放置一个缩窄器。其中4头猪在12周后额外接受了CABG，使用左乳内动脉移植到缩窄器远端的LAD。5头猪放置了缩窄器但未接受CABG（冬眠组）。5头猪未放置缩窄器（对照组）。使用计算机断层血管造影术确认缩窄器放置部位的狭窄以及左乳内动脉移植物的通畅情况。在基线和40μg/kg/min多巴酚丁胺输注期间测定局部血流。通过蛋白质印迹法对线粒体蛋白进行定量。
在多巴酚丁胺输注期间，CABG后LAD区域的血流低于远离区域（2.54±0.24对3.46±0.33mL/min/g；P<0.05）。与对照组相比，冬眠组的电子传递链蛋白降低约70%，并且在CABG后未能恢复正常。CABG后，与冬眠组相比，PGC1α核结合含量增加（分别为9.02±0.48对5.54±0.98任意单位；P<0.05），线粒体融合蛋白1和2以及视神经萎缩蛋白1的表达增加了一倍多。
冬眠心脏在CABG后4周时PGC1α和线粒体融合蛋白增加，表明线粒体融合已经开始发生并预示着线粒体早期恢复。未来的研究应探讨相对于线粒体蛋白表达的最大心肌氧消耗的变化。
